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Abstract The virus life cycle depends on host-virus protein-protein interactions, which often involve a disordered protein region binding to a folded protein domain. Here, we used proteomic peptide phage display (ProP-PD) to identify peptides from the intrinsically disordered regions of the human proteome that bind to folded protein domains encoded by the SARS-CoV-2 genome. Eleven folded domains of SARS-CoV-2 proteins were found to bind 281 peptides from human proteins, and affinities of 31 interactions involving eight SARS-CoV-2 protein domains were determined (K D ∼ 7-300 μM). Key specificity residues of the peptides were established for six of the interactions. Two of the peptides, binding Nsp9 and Nsp16, respectively, inhibited viral replication. Our findings demonstrate how high-throughput peptide binding screens simultaneously identify potential host-virus interactions and peptides with antiviral properties. Furthermore, the high number of low-affinity interactions suggest that overexpression of viral proteins during infection may perturb multiple cellular pathways.

Extensive problematic school absenteeism is a growing problem in Swedish schools. This means serious consequences both for the child and for society at large. This makes it essential to carry out a study where the voices of students and teachers are heard. This study identified and analyzed the risk and protective factors expressed by teachers and students regarding extensive problematic school absenteeism. The students are found within the autism spectrum, something that is common when it comes to students who are absent from school. The Semi-structured interviews were conducted and analyzed through reflexive thematic content analysis. The results showed that students' and teachers' perceptions were consistent and distinctive. Structure, learning environment, and relationships were the themes that emerged most clearly during the analysis.

Abstract Viruses mimic host short linear motifs (SLiMs) to hijack and deregulate cellular functions. Studies of motif-mediated interactions therefore provide insight into virus-host dependencies, and reveal targets for therapeutic intervention. Here, we describe the pan-viral discovery of 1712 SLiM-based virus-host interactions using a phage peptidome tiling the intrinsically disordered protein regions of 229 RNA viruses. We find mimicry of host SLiMs to be a ubiquitous viral strategy, reveal novel host proteins hijacked by viruses, and identify cellular pathways frequently deregulated by viral motif mimicry. Using structural and biophysical analyses, we show that viral mimicry-based interactions have similar binding strength and bound conformations as endogenous interactions. Finally, we establish polyadenylate-binding protein 1 as a potential target for broad-spectrum antiviral agent development. Our platform enables rapid discovery of mechanisms of viral interference and the identification of potential therapeutic targets which can aid in combating future epidemics and pandemics.

Reconstruction of an ancient nuclear coactivator binding domain (NCBD) of CREB-binding protein from a bilaterian animal ancestor living 600 million years ago reveals conserved dynamic properties in human NCBD.

Abstract Specific protein–protein interactions are central to all processes that underlie cell physiology. Numerous studies have together identified hundreds of thousands of human protein–protein interactions. However, many interactions remain to be discovered, and low affinity, conditional, and cell type‐specific interactions are likely to be disproportionately underrepresented. Here, we describe an optimized proteomic peptide‐phage display library that tiles all disordered regions of the human proteome and allows the screening of ~ 1,000,000 overlapping peptides in a single binding assay. We define guidelines for processing, filtering, and ranking the results and provide PepTools, a toolkit to annotate the identified hits. We uncovered >2,000 interaction pairs for 35 known short linear motif (SLiM)‐binding domains and confirmed the quality of the produced data by complementary biophysical or cell‐based assays. Finally, we show how the amino acid resolution‐binding site information can be used to pinpoint functionally important disease mutations and phosphorylation events in intrinsically disordered regions of the proteome. The optimized human disorderome library paired with PepTools represents a powerful pipeline for unbiased proteome‐wide discovery of SLiM‐based interactions.

Many interactions between viral and host proteins are mediated by short peptide motifs. Here, using a phage-based viral peptide library, the authors identify 269 peptide-based interactions for 18 coronaviruses, including an interaction between SARS-CoV-2 N and G3BP1/2 that affects stress granules.

Precocious male maturation causes reduced welfare and increased production costs in Atlantic salmon (Salmo salar) aquaculture. The pituitary produces and releases follicle-stimulating hormone (Fsh), the gonadotropin triggering puberty in male salmonids. However, little is known about how Fsh production is regulated in Atlantic salmon. We examined, in vivo and ex vivo, transcriptional changes of gonadotropin-related genes accompanying the initial steps of testis maturation, in pituitaries of males exposed to photoperiod and temperature conditions promoting maturation (constant light and 16°C). Pituitary fshb, lhb and gnrhr2bba transcripts increased in vivo in maturing males (gonado-somatic index > 0.1%). RNA sequencing (RNAseq) analysis using pituitaries from genetically similar males carrying the same genetic predisposition to mature, but differing by responding or not responding to stimulatory environmental conditions, revealed 144 differentially expressed genes, ~2/3rds being up-regulated in responders, including fshb and other pituitary hormones, steroid-related and other puberty-associated transcripts. Functional enrichment analyses confirmed gene involvement in hormone/steroid production and gonad development. In ex vivo studies, whole pituitaries were exposed to a selection of hormones and growth factors. Gonadotropin-releasing hormone (Gnrh), 17β-estradiol (E2) and 11-ketotestosterone (11-KT) up-regulated gnrhr2bba and lhb, while fshb was up-regulated by Gnrh but down-regulated by 11-KT in pituitaries from immature males. Also pituitaries from maturing males responded to Gnrh and sex steroids by increased gnrhr2bba and lhb transcript levels, but fshb expression remained unchanged. Growth factors (inhibin A, activin A and insulin-like growth factor 1) did not change gnrhr2bba, lhb or fshb transcript levels in pituitaries either from immature or maturing males. Additional pituitary ex vivo studies on candidates identified by RNAseq showed that these transcripts were preferentially regulated by Gnrh and sex steroids, but not by growth factors, and that Gnrh/sex steroids were less effective when incubating pituitaries from maturing males. Our results suggest that a yet to be characterized mechanism up-regulating fshb expression in the salmon pituitary is activated in response to stimulatory environmental conditions prior to morphological signs of testis maturation, and that the transcriptional program associated with this mechanism becomes unresponsive or less responsive to most stimulators ex vivo once males had entered pubertal developmental in vivo.

OBJECTIVE: The aim was to study the impact of metabolic syndrome on the risk for disability pension among Swedish employees. METHODS: A working population-based prospective cohort [Work, Lipids and Fibrinogen (WOLF) cohort, N=10 803], was linked to national registry records of all-cause disability pension for the period 1992–2013. Occupational health service data included 1992–2009 anthropometric measurements, blood samples, and questionnaires. Metabolic syndrome was defined according to International Diabetes Federation criteria, and risk for any all-cause disability pension was analyzed using Cox proportional hazard regression as hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, sex and other covariates. RESULTS: Of the employees, 17.9% (men 21.5%, women 9.7%) met the criteria for metabolic syndrome. The prevalence of all-cause disability pension was 15.2% in men with metabolic syndrome and 7.5% in men without metabolic syndrome; for women, the corresponding results were 23.2% and 12.7%. After adjustment for socio-demographic factors, health behaviors, work-related factors, diabetes, and obesity, the risk for all-cause disability pension among subjects with metabolic syndrome displayed an HR of 1.37 (95% CI 1.18–1.60). Results were similar for men and women. In a subgroup, further adjustment for chronic diseases resulted in an HR of 1.32 (95% CI 1.04–1.68). CONCLUSION: This study demonstrates an increased risk for all-cause disability pension, even after adjustment for other risk factors, among Swedish employees with metabolic syndrome compared to those without at baseline.

Following the publication of our article [1], we have become aware of one error in the exclusion criteria, inconsistencies in Figure 1 and Figure 2, and a typo in the reference list.

Abstract Background Sustainability challenges are currently hampering an increase in salmon production. Using sterile salmon can solve problems with precocious puberty and genetic introgression from farmed escapees to wild populations. Recently sterile salmon was produced by knocking out the germ cell-specific dead end (dnd). Several approaches may be applied to inhibit Dnd function, including gene knockout, knockdown or immunization. Since it is challenging to develop a successful treatment against a gene product already existing in the body, alternative targets are being explored. Germ cells are surrounded by, and dependent on, gonadal somatic cells. Targeting genes essential for the survival of gonadal somatic cells may be good alternative targets for sterility treatments. Our aim was to identify and characterize novel germ cell and gonadal somatic factors in Atlantic salmon. Results We have for the first time analysed RNA-sequencing data from germ cell-free (GCF)/dnd knockout and wild type (WT) salmon testis and searched for genes preferentially expressed in either germ cells or gonadal somatic cells. To exclude genes with extra-gonadal expression, our dataset was merged with available multi-tissue transcriptome data. We identified 389 gonad specific genes, of which 194 were preferentially expressed within germ cells, and 11 were confined to gonadal somatic cells. Interestingly, 5 of the 11 gonadal somatic transcripts represented genes encoding secreted TGF-β factors; gsdf, inha, nodal and two bmp6-like genes, all representative vaccine targets. Of these, gsdf and inha had the highest transcript levels. Expression of gsdf and inha was further confirmed to be gonad specific, and their spatial expression was restricted to granulosa and Sertoli cells of the ovary and testis, respectively. Finally, we show that inha expression increases with puberty in both ovary and testis tissue, while gsdf expression does not change or decreases during puberty in ovary and testis tissue, respectively. Conclusions This study contributes with transcriptome data on salmon testis tissue with and without germ cells. We provide a list of novel and known germ cell- and gonad somatic specific transcripts, and show that the expression of two highly active gonadal somatic secreted TGF-β factors, gsdf and inha, are located within granulosa and Sertoli cells.

Background: Perfluorinated substances (PFAS) are chemicals with endocrine disruptive properties that may interfere with the female reproductive system. However, few studies have explored the association between benign gynecological diseases and high PFAS exposure. Objectives: The aim of this study was to investigate the possible associations between PFAS exposure and subsequent diagnosis of polycystic ovarian syndrome (PCOS), uterine leiomyoma (fibroids), and endometriosis in a cohort exposed to PFAS through drinking water. Material and methods: In 2013, high levels (with sum of PFAS above 10,000 ng/L), dominated by perfluorooctanesulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), were found in the drinking water from one of the two waterworks in Ronneby, Sweden. The contamination came from firefighting foams used at a nearby airfield. Females of all ages (n = 29,106) who had ever resided in the municipality between 1985 and 2013 formed a cohort. Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential address data; 27% of the females had ever lived at an address with PFAS-contaminated water. Gynecological health outcomes were retrieved from the Swedish National Patient Register. The Cox proportional hazards model was used to estimate the association between exposure and each diagnosis. Results: There were in all 161 cases of PCOS, 1,122 cases of uterine leiomyoma, and 373 cases of endometriosis. In women aged 20–50 years (n = 18,503), those with the highest estimated PFAS exposure had increased hazard ratios (HR) for PCOS (HR = 2.18; 95% confidence interval (CI) 1.43, 3.34) and uterine leiomyoma (HR = 1.28; 95% CI 0.95, 1.74). No increased HR for endometriosis was found (HR = 0.74; 95% CI 0.42, 1.29). Conclusions: Exposure to high levels of PFAS in drinking water was associated with increased risk of PCOS and possibly uterine leiomyoma, but not endometriosis. The findings for PCOS are consistent with prior studies reporting positive associations between PCOS and PFAS exposure at background levels.

Textile research has demonstrated that new types of textiles were introduced to Scandinavia in the latter part of the Scandinavian Iron Age (AD 700–900). The archaeology of the period displays an increased number of textile tools, and large concentrations of pit houses dedicated to textile production. This era also saw the introduction of sails to Scandinavia, which is one of the obvious reasons for textiles and textile production becoming such an important part of Viking Age society. However, hitherto the value of the textiles has mostly been ignored, and its impact rarely discussed in research. This article will attempt to remedy this and poses important questions, such as: what was the economic value of the textiles needed for travel and warfare, and what was the value of the textiles used on a journey? In the article, the 10th century Ladby ship from Fyn in Denmark, is used to exemplify the demands and economic value of all textiles of one single ship, on one journey. I will use an interdisciplinary approach, including analyses of archaeological textiles; iconography; and early medieval texts. The aim of this novel method is to highlight the importance of textiles. It will also explore how journeys under sail and warfare contributed to the increased consumption of textiles.

Abstract Background Puberty in male Atlantic salmon in aquaculture can start as early as after the first winter in seawater, stunts growth and entails welfare problems due to the maturation-associated loss of osmoregulation capacity in seawater. A better understanding of the regulation of puberty is the basis for developing improved cultivation approaches that avoid these problems. Our aim here was to identify morphological and molecular markers signaling the initiation of, and potential involvement in, testis maturation. Methods In the first experiment, we monitored for the first time in large Atlantic salmon males several reproductive parameters during 17 months including the first reproductive cycle. Since testicular growth accelerated after the Winter solstice, we focused in the second experiment on the 5 months following the winter solstice, exposing fish from February 1 onwards to the natural photoperiod (NL) or to continuous additional light (LL). Results In the first experiment, testis weight, plasma androgens and pituitary gonadotropin transcript levels increased with the appearance of type B spermatogonia in the testis, but testicular transcript levels for gonadotropin or androgen receptors did not change while being clearly detectable. In the second experiment, all males kept under NL had been recruited into puberty until June. However, recruitment into puberty was blocked in ~ 40% of the males exposed to LL. The first morphological sign of recruitment was an increased proliferation activity of single spermatogonia and Sertoli cells. Irrespective of the photoperiod, this early sign of testis maturation was accompanied by elevated pituitary gnrhr4 and fshb and testicular igf3 transcript levels as well as increased plasma androgen levels. The transition into puberty occurred again with stable testicular gonadotropin and androgen receptor transcript levels. Conclusions The sensitivity to reproductive hormones is already established before puberty starts and up-regulation of testicular hormone receptor expression is not required to facilitate entry into puberty. The increased availability of receptor ligands, on the other hand, may result from an up-regulation of pituitary Gnrh receptor expression, eventually activating testicular growth factor and sex steroid release and driving germ and Sertoli cell proliferation and differentiation.

Abstract Background When puberty starts before males reach harvest size, animal welfare and sustainability issues occur in Atlantic salmon (Salmo salar) aquaculture. Hallmarks of male puberty are an increased proliferation activity in the testis and elevated androgen production. Examining transcriptional changes in salmon testis during the transition from immature to maturing testes may help understanding the regulation of puberty, potentially leading to procedures to modulate its start. Since differences in body weight influence, via unknown mechanisms, the chances for entering puberty, we used two feed rations to create body weight differences. Results Maturing testes were characterized by an elevated proliferation activity of Sertoli cells and of single undifferentiated spermatogonia. Pituitary gene expression data suggest increased Gnrh receptor and gonadotropin gene expression, potentially responsible for the elevated circulating androgen levels in maturing fish. Transcriptional changes in maturing testes included a broad variety of signaling systems (e.g. Tgfβ, Wnt, insulin/Igf, nuclear receptors), but also, activation of metabolic pathways such as anaerobic metabolism and protection against ROS. Feed restriction lowered the incidence of puberty. In males maturing despite feed restriction, plasma androgen levels were higher than in maturing fish receiving the full ration. A group of 449 genes that were up-regulated in maturing fully fed fish, was up-regulated more prominently in testis from fish maturing under caloric restriction. Moreover, 421 genes were specifically up-regulated in testes from fish maturing under caloric restriction, including carbon metabolism genes, a pathway relevant for nucleotide biosynthesis and for placing epigenetic marks. Conclusions Undifferentiated spermatogonia and Sertoli cell populations increased at the beginning of puberty, which was associated with the up-regulation of metabolic pathways (e.g. anaerobic and ROS pathways) known from other stem cell systems. The higher androgen levels in males maturing under caloric restriction may be responsible for the stronger up-regulation of a common set of (449) maturation-associated genes, and the specific up-regulation of another set of (421) genes. The latter opened regulatory and/or metabolic options for initiating puberty despite feed restriction. As a means to reduce the incidence of male puberty in salmon, however, caloric restriction seems unsuitable.

Abstract Background In Atlantic salmon in the wild, age at maturity is strongly influenced by the vgll3 locus. Under farming conditions, light, temperature and feeding regimes are known significantly advance or delay age at maturity. However, the potential influence of the vgll3 locus on the maturation of salmon reared under farming conditions has been rarely investigated, especially in females. Results Here, we reared domesticated salmon (mowi strain) with different vgll3 genotypes under standard farming conditions until they matured at either one, two or more than two sea winters. Interestingly, and in contrast to previous findings in the wild, we were not able to identify a link between vgll3 and age at maturity in females when reared under farming conditions. For males however, we found that the probability of delaying maturation from one to two sea winters was significantly lower in fish homozygous for the early allele compared to homozygous fish for the late allele, while the probability for heterozygous fish was intermediate. These data also contrast to previous findings in the wild where the early allele has been reported as dominant. However, we found that the probability of males delaying maturation from two to three sea winters was regulated in the same manner as the wild. Conclusions Collectively, our data suggest that increased growth rates in mowi salmon, caused by high feed intake and artificial light and temperature regimes together with other possible genetic/epigenetic components, may significantly influence the impact that the vgll3 locus has on age at maturity, especially in females. In turn, our results show that the vgll3 locus can only to a large extent be used in selective breeding to control age at maturation in mowi males. In summary, we here show that in contrast to the situation in wild salmon, under farming conditions vgll3 does not seem to influence age at maturity in mowi females whereas in mowi males, maturing as one or two sea winters it alters the early allele effect from dominant to intermediate.

Abstract Background Generalised anxiety disorder (GAD) is a frequent and severe anxiety disorder among older adults. GAD increases the risk of developing other disorders such as depression and coronary heart disease. Older adults with GAD exhibit a poorer response to cognitive behaviour therapy (CBT) compared to younger patients with GAD. The normal age-related cognitive decline can be a contributor to reduced treatment efficacy. One strategy for improving treatment efficacy is to combine CBT with adjunctive interventions targeted at improving cognitive functions. Physical exercise is a viable intervention in this regard. Increased levels of brain-derived neurotrophic factor may mediate improvement in cognitive function. The present study aims to investigate the proposed effects and mechanisms related to concomitant physical exercise. Methods The sample comprises 70 participants aged 60–75 years, who have GAD. Exclusion criteria comprise substance abuse and unstable medication; inability to participate in physical exercise; and conditions which precludes GAD as primary diagnosis. The interventions are individual treatment in the outpatient clinic at the local psychiatric hospital, with two experimental arms: (1) CBT + physical exercise and (2) CBT + telephone calls. The primary outcome measure is symptom reduction on the Penn State Worry Questionnaire. Other measures include questionnaires, clinical interviews, physiological, biological and neuropsychological tests. A subset of 40 participants will undergo magnetic resonance imaging (MRI). After inclusion, participants undergo baseline testing, and are subsequently randomized to a treatment condition. Participants attend five sessions of the add-on treatment in the pre-treatment phase, and move on to interim testing. After interim testing, participants attend 10 sessions of CBT in parallel with continued add-on treatment. Participants are tested post-intervention within 2 weeks of completing treatment, with follow-up testing 6 and 12 months later. Discussion This study aims to develop better treatment for GAD in older adults. Enhancing treatment response will be valuable from both individual and societal perspectives, especially taking the aging of the general population into account. Trial registration ClinicalTrials.gov, NCT02690441. Registered on 24 February 2016.

Abstract Background Sedentary behaviour has been closely linked to metabolic and cardiovascular health and is therefore of importance in disease prevention. A user-friendly tool for assessment of sitting time is thus needed. Previous studies concluded that the present tools used to assess a number of sedentary behaviours are more likely to overestimate sitting than single-item questions which often underestimate sitting time, and that categorical answering options are recommended. In line with this, the single-item question with categorical answering options, SED-GIH, was developed. The aim of this study was to investigate the criterion validity of the SED-GIH question using activPAL3 micro as the criterion measure. The second aim was to evaluate the test-retest reliability of the SED-GIH questionnaire. Method In the validity section of this study, 284 middle-aged adults answered a web questionnaire, which included SED-GIH, wore activPAL and filled in a diary log for one week. Spearman’s rho assessed the relationship between the SED-GIH answers and the daily average sitting time as monitored by the activPAL (activPAL-SIT), a Weighted Kappa assessed the agreement, ANOVA assessed differences in activPAL-SIT between the SED-GIH answer categories, and a Chi2 compared the proportions of hazardous sitters between the different SED-GIH answer categories. In the reliability section, 95 elderly participants answered the SED-GIH question twice, with a mean interval of 5.2 days. The reliability was assessed with ICC and a weighted Kappa. Results The SED-GIH question correlated moderately with activPAL-SIT (rho = 0.31), with a poor agreement (weighted Kappa 0.12). In total, 40.8% underestimated and 22.2% overestimated their sitting time. The ANOVA showed significant differences in activPAL-SIT between the different SED-GIH answer categories (p

Entering meiosis strictly depends on stimulated by retinoic acid 8 (Stra8) gene function in mammals. This gene is missing in a number of fish species, including medaka and zebrafish, but is present in the majority of fishes, including Atlantic salmon. Here, we have examined the effects of removing stra8 on male fertility in Atlantic salmon. As in mammals, stra8 expression was restricted to germ cells in the testis, transcript levels increased during the start of puberty, and decreased when blocking the production of retinoic acid. We targeted the salmon stra8 gene with two gRNAs one of these were highly effective and produced numerous mutations in stra8, which led to a loss of wild-type (WT) stra8 expression in F0 salmon testis. In maturing stra8 crispants, the spermatogenetic tubuli were partially disorganized and displayed a sevenfold increase in germ cell apoptosis, in particular among type B spermatogonia and spermatocytes. The production of spermatogenic cysts, on the other hand, increased in maturing stra8 crispants. Gene expression analysis revealed unchanged (lin28a, ret) or reduced levels (egr1, dusp4) of transcripts associated with undifferentiated spermatogonia. Decreased expression was recorded for some genes expressed in differentiating spermatogonia including dmrt1 and ccnd2 or in spermatocytes, such as ccna1. Different from Stra8-deficient mammals, a large number of germ cells completed spermatogenesis, sperm was produced and fertilization rates were similar in WT and crispant males. While loss of stra8 increased germ cell apoptosis during salmon spermatogenesis, crispants compensated this cell loss by an elevated production of spermatogenic cysts, and were able to produce functional sperm. It appears that also in a fish species with a stra8 gene in the genome, the critical relevance this gene has attained for mammalian spermatogenesis is not yet given, although detrimental effects of the loss of stra8 were clearly visible during maturation.

PurposeThe aim was to examine potential associations between psychosocial job exposures, evaluated with the Job Demand-Control-model, and presence of coronary artery calcium.MethodsWe performed a cross-sectional study using the Swedish CArdioPulmonary bioImage Study,(SCAPIS)pilot study. Coronary artery calcium was assessed through computed tomography of the coronary arteries and with coronary artery scoring, CACS. Main outcome was CACS ≥100 compared to CACS 0. Job demand and control was analysed according to the standard categorization of the two variables into: high strain, active, passive and low strain (reference). Associations between these variables and CACS were calculated with prevalence ratios (PR) using Cox regression with robust variance, 95% confidence intervals (CI) and adjusted for age, smoking, education, socioeconomic area and metabolic syndrome.ResultsIn total 777 participants were used in our analyses, for which 20% of the men and 5% of the women had CACS ≥100, respectively. The PR of having CACS ≥100 was non-significantly elevated for men in high strain jobs 1.54 (95% CI 0.88-2.69) and in active jobs 1.67 (95% CI 0.92-3.06), adjusted for covariates. For women there was no association between exposure to high strain and having CACS ≥100 PR 1.02 (95% CI 0.24-4.31). Among women reporting passive job, the PR was non-significantly elevated, 2.40 (95% CI 0.83-6.92), adjusted for covariates.ConclusionThe statistical power of the study was limited, but our results suggests the possibility that exposure to a high strain or an active job situation may increase the risk of CACS in men, while in women, it may rather be exposure to passive job.

Ankle plantar flexor muscles are active in the stance phase of walking to propel the body forward. Increasing walking speed requires increased plantar flexor excitation, frequently assessed using surface electromyography (EMG). Despite its popularity, validity of surface EMG applied on shank muscles is mostly unclear. Thus, we examined the agreement between surface and intramuscular EMG at a range of walking speeds. Ten participants walked overground at slow, preferred, fast, and maximum walking speeds (1.01 ± 0.13, 1.43 ± 0.19, 1.84 ± 0.23, and 2.20 ± 0.38 m s–1, respectively) while surface and fine-wire EMG activities of flexor hallucis longus (FHL), soleus (SOL), medial gastrocnemius (MG) and lateral gastrocnemius (LG), and tibialis anterior (TA) muscles were recorded. Surface and intramuscular peak-normalised EMG amplitudes were compared for each muscle and speed across the stance phase using Statistical Parametric Mapping. In FHL, we found differences around peak activity at all speeds except fast. There was no difference in MG at any speed or in LG at slow and preferred speeds. For SOL and LG, differences were seen in the push-off phase at fast and maximum walking speeds. In SOL and TA, surface EMG registered activity during phases in which intramuscular EMG indicated inactivity. Our results suggest that surface EMG is generally a suitable method to measure MG and LG EMG activity across several walking speeds. Minimising cross-talk in FHL remains challenging. Furthermore, SOL and TA muscle onset/offset defined by surface EMG should be interpreted cautiously. These findings should be considered when recording and interpreting surface EMG of shank muscles in walking.

The purpose of this study was to describe the effect of increasing workload on individual thigh muscle activation during a 20 minute incremental cycling test. Intramuscular electromyographic signals were recorded from the knee extensors rectus femoris, vastus lateralis, vastus medialis and vastus intermedius and the knee flexors semimembranosus, semitendinosus, and the short and long heads of the biceps femoris during increasing workloads. Mean activation levels were compared over the whole pedaling cycle and the crank angles at which onset and offset of activation and peak activity occurred were identified for each muscle. These data were compared between three workloads. EMG activation level significantly increased (p

Following publication of the original article [1], the authors would like to apologize for an error in Fig. 5e, the correct graph is presented below and shows the significant increase in pituitary mRNA levels of fshb in recruited males in the SGA stage.

Protein-protein interactions involving intrinsically disordered proteins are important for cellular function and common in all organisms. However, it is not clear how such interactions emerge and evolve on a molecular level. We performed phylogenetic reconstruction, resurrection and biophysical characterization of two interacting disordered protein domains, CID and NCBD. CID appeared after the divergence of protostomes and deuterostomes 450–600 million years ago, while NCBD was present in the protostome/deuterostome ancestor. The most ancient CID/NCBD formed a relatively weak complex (Kd∼5 µM). At the time of the first vertebrate-specific whole genome duplication, the affinity had increased (Kd∼200 nM) and was maintained in further speciation. Experiments together with molecular modeling using NMR chemical shifts suggest that new interactions involving intrinsically disordered proteins may evolve via a low-affinity complex which is optimized by modulating direct interactions as well as dynamics, while tolerating several potentially disruptive mutations.